Annals of Epidemiology 25 (2015) 40e45
Contents lists available at ScienceDirect
Annals of Epidemiology journal homepage: www.annalsofepidemiology.org
Original article
Preterm birth and long-term maternal cardiovascular health Wei Perng PhD, MPH a, *, Jennifer Stuart MSc b, Sheryl L. Rifas-Shiman MPH a, Janet W. Rich-Edwards ScD, MPH c, Alison Stuebe MD d, Emily Oken MD, MPH a, e a
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA Department of Epidemiology, Harvard School of Public Health, Boston, MA c Connors Center for Women’s Health, Brigham and Women’s Hospital, Boston, MA d Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill e Department of Nutrition, Harvard School of Public Health, Boston, MA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 July 2014 Accepted 13 October 2014 Available online 18 October 2014
Purpose: To investigate whether preterm birth (PTB) is associated with greater cardiovascular disease (CVD) risk in a longitudinal cohort. Methods: We examined differences in systolic blood pressure (SBP), diastolic blood pressure, insulin resistance (Homeostatic model assessment of insulin resistance), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, C-reactive protein, and interleukin 6 at 3 years postpartum between women who delivered preterm (gestation 140 mm Hg or DBP >90 mm Hg) before 20 weeks of gestation. We
42
W. Perng et al. / Annals of Epidemiology 25 (2015) 40e45
categorized a woman as having gestational hypertension if she did not have chronic hypertension but developed elevated SBP (>140 mm Hg) or DBP (>90 mm Hg) on two or more occasions after 20 weeks of gestation. We classified women as having preeclampsia if they did not have chronic hypertension but developed increased blood pressure as just defined in addition to proteinuria (dipstick value of 1 þ on two or more occasions or 2 once) more than 4 hours but 7 days or less or less apart or if they had chronic hypertension and developed proteinuria after 20 weeks of gestation. Data analysis To identify potential confounders to the relation of PTB with the maternal outcomes, we examined the distribution of PTB prevalence across categories of sociodemographic, lifestyle, and peripartum characteristics. We evaluated the statistical significance of the associations with the Wald chi-squared statistic for categorical variables and a test of linear trend for ordinal variables. Next, we estimated mean differences and 95% confidence intervals (CI) for maternal cardiovascular risk markers (SBP, DBP, total cholesterol, HDL, LDL, triglycerides, HOMA-IR, CRP, and IL-6) at 3 years postpartum for women who had a PTB versus those who delivered at term. For blood pressure, we focused on results for SBP because it is a better predictor of long-term outcomes [20] and is more accurately measured than DBP [21]. Biomarkers that were not normally distributed (triglycerides, HOMA-IR, CRP, and IL-6) were natural log (ln)-transformed before use in the regression models. In multivariable analyses, we constructed a series of models that first accounted for nonmodifiable characteristics (model 1: maternal age and race/ethnicity), followed by sociodemographic and perinatal factors (model 2: model 1 þ prepregnancy BMI, parity, marital status, and education level), followed by hypertensive disorders of pregnancy (model 3), which were previously reported to predict postpartum cardiometabolic health [10]. Model 2 for blood pressure also included the first clinically measured SBP during the first trimester, and model 3 for HOMA-IR also included gestational glucose tolerance, in four categories. We used the same set of models to examine associations with the maternal adiposity indicators (BMI, weight change from prepregnancy weight, and waist circumference) at 3 and 7 years postpartum. The adjustment covariates were selected based on bivariate associations and our a priori knowledge of CVD risk factors. We also examined associations after accounting for lifestyle characteristics (diet, physical activity, and smoking habits at the postpartum time points) that could influence the maternal outcomes, which resulted in no material difference in the estimates, so these variables were not included in final models. Excluding four mothers who had a planned PTB (based on indication of planned Cesarean section, as opposed to an unplanned Cesarean section or vaginal birth) yielded no difference in the results. We also examined the associations with SBP after excluding women with chronic hypertension and those with a prepregnancy hypertensive history and observed no substantial differences in the direction, magnitude, or precision of the associations; thus, we included all women in the analysis and report these estimates separately in text. In sensitivity analyses, we further accounted for maternal lifestyle characteristics at each of the postpartum time points, including smoking status, physical activity, and diet. The results were essentially unchanged after inclusion of these variables, so they were not included in the final models. All analyses were performed with SAS software (version 9.3; SAS Institute Inc., Cary, NC).
Table 1 Occurrence of PTB (gestational age
Contents lists available at ScienceDirect
Annals of Epidemiology journal homepage: www.annalsofepidemiology.org
Original article
Preterm birth and long-term maternal cardiovascular health Wei Perng PhD, MPH a, *, Jennifer Stuart MSc b, Sheryl L. Rifas-Shiman MPH a, Janet W. Rich-Edwards ScD, MPH c, Alison Stuebe MD d, Emily Oken MD, MPH a, e a
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA Department of Epidemiology, Harvard School of Public Health, Boston, MA c Connors Center for Women’s Health, Brigham and Women’s Hospital, Boston, MA d Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill e Department of Nutrition, Harvard School of Public Health, Boston, MA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 July 2014 Accepted 13 October 2014 Available online 18 October 2014
Purpose: To investigate whether preterm birth (PTB) is associated with greater cardiovascular disease (CVD) risk in a longitudinal cohort. Methods: We examined differences in systolic blood pressure (SBP), diastolic blood pressure, insulin resistance (Homeostatic model assessment of insulin resistance), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, C-reactive protein, and interleukin 6 at 3 years postpartum between women who delivered preterm (gestation 140 mm Hg or DBP >90 mm Hg) before 20 weeks of gestation. We
42
W. Perng et al. / Annals of Epidemiology 25 (2015) 40e45
categorized a woman as having gestational hypertension if she did not have chronic hypertension but developed elevated SBP (>140 mm Hg) or DBP (>90 mm Hg) on two or more occasions after 20 weeks of gestation. We classified women as having preeclampsia if they did not have chronic hypertension but developed increased blood pressure as just defined in addition to proteinuria (dipstick value of 1 þ on two or more occasions or 2 once) more than 4 hours but 7 days or less or less apart or if they had chronic hypertension and developed proteinuria after 20 weeks of gestation. Data analysis To identify potential confounders to the relation of PTB with the maternal outcomes, we examined the distribution of PTB prevalence across categories of sociodemographic, lifestyle, and peripartum characteristics. We evaluated the statistical significance of the associations with the Wald chi-squared statistic for categorical variables and a test of linear trend for ordinal variables. Next, we estimated mean differences and 95% confidence intervals (CI) for maternal cardiovascular risk markers (SBP, DBP, total cholesterol, HDL, LDL, triglycerides, HOMA-IR, CRP, and IL-6) at 3 years postpartum for women who had a PTB versus those who delivered at term. For blood pressure, we focused on results for SBP because it is a better predictor of long-term outcomes [20] and is more accurately measured than DBP [21]. Biomarkers that were not normally distributed (triglycerides, HOMA-IR, CRP, and IL-6) were natural log (ln)-transformed before use in the regression models. In multivariable analyses, we constructed a series of models that first accounted for nonmodifiable characteristics (model 1: maternal age and race/ethnicity), followed by sociodemographic and perinatal factors (model 2: model 1 þ prepregnancy BMI, parity, marital status, and education level), followed by hypertensive disorders of pregnancy (model 3), which were previously reported to predict postpartum cardiometabolic health [10]. Model 2 for blood pressure also included the first clinically measured SBP during the first trimester, and model 3 for HOMA-IR also included gestational glucose tolerance, in four categories. We used the same set of models to examine associations with the maternal adiposity indicators (BMI, weight change from prepregnancy weight, and waist circumference) at 3 and 7 years postpartum. The adjustment covariates were selected based on bivariate associations and our a priori knowledge of CVD risk factors. We also examined associations after accounting for lifestyle characteristics (diet, physical activity, and smoking habits at the postpartum time points) that could influence the maternal outcomes, which resulted in no material difference in the estimates, so these variables were not included in final models. Excluding four mothers who had a planned PTB (based on indication of planned Cesarean section, as opposed to an unplanned Cesarean section or vaginal birth) yielded no difference in the results. We also examined the associations with SBP after excluding women with chronic hypertension and those with a prepregnancy hypertensive history and observed no substantial differences in the direction, magnitude, or precision of the associations; thus, we included all women in the analysis and report these estimates separately in text. In sensitivity analyses, we further accounted for maternal lifestyle characteristics at each of the postpartum time points, including smoking status, physical activity, and diet. The results were essentially unchanged after inclusion of these variables, so they were not included in the final models. All analyses were performed with SAS software (version 9.3; SAS Institute Inc., Cary, NC).
Table 1 Occurrence of PTB (gestational age
